The Journal of clinical endocrinology and metabolism · 2025
Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome.
СтатьяКлиническое исследование III фазыРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Haqq Andrea M, Poitou Christine, Chung Wendy K, Forsythe Elizabeth, Conroy Rushika, Dollfus Hélène, Malhotra Sonali, Touchot Nicolas, Okorie Uzoma, Beales Philip, Clément Karine, Argente Jesús
Аннотация
CONTEXT: Bardet-Biedl syndrome (BBS) is a rare genetic disease associated with disruptions in melanocortin-4 receptor pathway signaling that can contribute to increased risk for metabolic syndrome and obesity-related comorbidities.
OBJECTIVE: Here, MetS-Z-BMI scores, a continuous measure based on body mass index (BMI), were calculated to determine metabolic syndrome severity and response to treatment with the melanocortin-4 receptor agonist setmelanotide in BBS.
METHODS: All patients from a phase 3 study (NCT03746522) of setmelanotide with data required for the calculation of MetS-Z-BMI scores were included. Mean MetS-Z-BMI score was determined at baseline and Week 52; subgroup analyses were conducted by sex, age, genotype, and response to setmelanotide.
RESULTS: MetS-Z-BMI scores were evaluable for 22 of 32 patients enrolled. Baseline mean (SD) MetS-Z-BMI score across patients was 1.1 (0.5); baseline mean (SD) odds ratios of future cardiovascular disease or type 2 diabetes were 3.1 (1.5) and 3.7 (1.7), respectively, for adults and 10.2 (4.7) and 2.8 (1.3), respectively, for pediatric patients. Overall, mean (SD) MetS-Z-BMI score at Week 52 was reduced by 0.34 (0.62). Mean (SD) MetS-Z-BMI scores significantly differed depending on achievement of predetermined weight-based thresholds of ≥10% weight loss (patients aged ≥18 years) or ≥0.3-point reduction in BMI Z score (patients aged <18 years) at Week 52 (achievers, -0.64 [0.54]; nonachievers, 0.08 [0.47]; P = .0043). No significant difference was observed with other subgroup comparisons.
CONCLUSION: MetS-Z-BMI score reductions were observed after 52 weeks of treatment, suggesting that setmelanotide may decrease metabolic syndrome severity and risk of future obesity-related comorbidities in those with BBS.
OBJECTIVE: Here, MetS-Z-BMI scores, a continuous measure based on body mass index (BMI), were calculated to determine metabolic syndrome severity and response to treatment with the melanocortin-4 receptor agonist setmelanotide in BBS.
METHODS: All patients from a phase 3 study (NCT03746522) of setmelanotide with data required for the calculation of MetS-Z-BMI scores were included. Mean MetS-Z-BMI score was determined at baseline and Week 52; subgroup analyses were conducted by sex, age, genotype, and response to setmelanotide.
RESULTS: MetS-Z-BMI scores were evaluable for 22 of 32 patients enrolled. Baseline mean (SD) MetS-Z-BMI score across patients was 1.1 (0.5); baseline mean (SD) odds ratios of future cardiovascular disease or type 2 diabetes were 3.1 (1.5) and 3.7 (1.7), respectively, for adults and 10.2 (4.7) and 2.8 (1.3), respectively, for pediatric patients. Overall, mean (SD) MetS-Z-BMI score at Week 52 was reduced by 0.34 (0.62). Mean (SD) MetS-Z-BMI scores significantly differed depending on achievement of predetermined weight-based thresholds of ≥10% weight loss (patients aged ≥18 years) or ≥0.3-point reduction in BMI Z score (patients aged <18 years) at Week 52 (achievers, -0.64 [0.54]; nonachievers, 0.08 [0.47]; P = .0043). No significant difference was observed with other subgroup comparisons.
CONCLUSION: MetS-Z-BMI score reductions were observed after 52 weeks of treatment, suggesting that setmelanotide may decrease metabolic syndrome severity and risk of future obesity-related comorbidities in those with BBS.